Adrenal Serenity by Natural Factors Stress-Relax

POSSIBLY EFFECTIVE

• Generalized anxiety disorder (GAD). Oral ashwagandha may modestly improve symptoms of anxiety in patients with GAD. Details: Clinical practice guidelines from the World Federation of Societies of Biological Psychiatry (WFSBP) and the Canadian Network for Mood and Anxiety Treatments (CANMAT) provisionally recommend ashwagandha root extract at doses of 300-600 mg, standardized to 5% withanolides, daily as monotherapy or adjunctive therapy in patients with GAD. This recommendation is based on a review of three preliminary clinical trials with consistent results (110318). Two of these studies are described below. A small clinical trial in patients with GAD who are taking selective serotonin reuptake inhibitors (SSRIs) shows that taking ashwagandha 1 gram daily for 6 weeks reduces symptoms of anxiety by 48%, compared with a 27% reduction in patients taking placebo. Furthermore, by the end of treatment, 72% of patients taking ashwagandha were determined to have mild symptoms of GAD, compared with only 32% of those taking placebo (102687). Another preliminary clinical trial in patients aged 16 years and older with GAD shows that taking ashwagandha root powder granules 4 grams three times daily for 60 days moderately improves anxious mood in 58% of patients, compared with no moderate improvement in the placebo group. Mild improvement occurred in 82% of patients in the placebo group and 40% of patients in the ashwagandha group (90654).
• Insomnia. Oral ashwagandha may modestly improve sleep in patients with insomnia or non-restorative sleep. Details: A small meta-analysis in patients with insomnia and healthy patients shows that taking a specific ashwagandha root extract (KSM-66, Ixoreal Biomed) 250-600 mg daily or a specific root and leaf extract (Shoden, Arjuna Natural) 120 mg daily for 6-12 weeks modestly improves overall sleep, as well as sleep quality, sleep latency, total sleep time, wake time after sleep onset, and sleep efficiency, when compared with placebo. Effects were more pronounced in those with insomnia, with doses of at least 600 mg daily, and with treatment durations of at least 8 weeks (106784). These findings may be limited by heterogeneity of the included studies. In patients with non-restorative sleep, clinical research shows that taking a specific ashwagandha extract (Shoden, Arjuna Natural Private Ltd) 125 mg daily for 6 weeks increases sleep quality by 72%, compared with an improvement of 29% in patients taking placebo. Small to moderate improvements also occurred in total sleep time, sleep latency, and number of times awake (103476).
• Stress. Oral ashwagandha seems to help reduce stress and may also reduce stress-related weight gain. Details: A meta-analysis of seven small clinical studies in healthy adults, patients with chronic stress, or patients with psychiatric conditions shows that taking ashwagandha 240-1000 mg daily for 8-12 weeks improves stress when compared with placebo (109587). Clinical studies included in this meta-analysis that evaluated adults with chronic stress show that taking specific ashwagandha root extracts 240 mg daily (Shoden, Arjuna Natural Ltd.) or 300 mg twice daily (KSM-66, Ixoreal Biomed) for 60 days reduces perceived stress levels by 30% to 44% and decreases cortisol levels by 22% to 28% when compared with baseline. These improvements remain significant when compared with the changes seen for patients treated with placebo (90652,95617,101816,102682). In adults reporting moderate to high stress levels, clinical research shows that treatment with specific slow-release capsules containing another ashwagandha root extract (Prolanza), 300 mg daily for 90 days, lowers perceived stress scores and cortisol levels when compared with placebo (107371). In healthy college students, clinical research also shows that taking ashwagandha root extract 350 mg twice daily for 30 days improves qualitative perceptions of stress management, but not stress scores, when compared with placebo (109589,109590). Other clinical research shows that taking ashwagandha root extract 500 mg twice daily may prevent stress-related weight gain when compared with placebo (95617).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Aging. A small clinical study suggests that oral ashwagandha may modestly improve well-being, sleep, and alertness in elderly patients. Details: A small clinical trial in individuals aged 65-80 years shows that taking ashwagandha root extract (KSM-66, Ixoreal Biomed) 600 mg daily for 12 weeks improves overall well-being, sleep quality, and mental alertness by small to moderate amounts when compared with placebo (102684).
• Antipsychotic-induced metabolic side effects. It is unclear if ashwagandha is beneficial for attenuating the metabolic side effects of antipsychotic agents. Details: One preliminary clinical trial shows that taking a specific ashwagandha extract (Cap Strelaxin, M/s Pharmanza Herbal Pvt. Ltd.) 400 mg three times daily for one month reduces serum triglycerides by 12% and fasting blood glucose by 15% when compared with baseline levels. Patients were taking atypical antipsychotics and had modestly elevated triglycerides and fasting blood glucose levels at baseline (90649). The validity of these findings is limited by the lack of a comparator group.
• Anxiety. It is unclear if oral ashwagandha is beneficial for reducing anxiety. Details: One small clinical study shows that taking ashwagandha root (Swiss Herbals) 300 mg twice daily for 12 weeks, in combination with standard psychotherapy interventions, including dietary counseling, deep breathing exercise instruction, and a multivitamin, reduces anxiety scores when compared with standard psychotherapy interventions and placebo (19271). However, other clinical research in young adults shows that a specific ashwagandha root and leaf extract (NooGandha, Specnova LLC) 225 mg or 400 mg daily for 30 days produces similar improvements in self-reported anxiety, stress, and depression scores when compared with placebo (107370).
• Asthma. Although there has been interest in using oral ashwagandha for asthma, there is insufficient reliable information about the clinical effects of ashwagandha for this condition.
• Athletic performance. It is unclear if ashwagandha is beneficial for improving athletic performance. Details: A meta-analysis of four small clinical trials shows that taking ashwagandha increases aerobic capacity in athletes and non-athletes based on the measurement of maximum oxygen consumption. Effective doses ranged from 500-1000 mg daily for up to 12 weeks (102683). Another meta-analysis shows that taking ashwagandha in doses of 120-1250 mg daily, as a single dose or divided twice daily, for up to 6 months seems to improve muscle strength, speed, time to exhaustion, recovery time, and cardiorespiratory fitness in athletes and non-athletes (105824). However, the validity of this analysis is reduced by the lack of a control group, the varied training levels of the subjects, and the wide range of outcomes assessed. More research is needed to determine whether taking ashwagandha can improve athletic performance.
• Attention deficit-hyperactivity disorder (ADHD). Oral ashwagandha has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: In a preliminary clinical trial, children with ADHD were given a combination herbal extract formula (Nurture & Clarity), containing ashwagandha, white peony root, gotu kola, blue-green algae, bacopa, and sage, 3 mL three times daily for 4 months. Measures of attention, cognition, and impulse control improved significantly in children receiving ashwagandha when compared with placebo (19272). The dose of ashwagandha in the combination product was not reported, and the effect of ashwagandha alone in ADHD is unclear.
• Back pain. Although there has been interest in using oral or topical ashwagandha for back pain, there is insufficient reliable information about the clinical effects of ashwagandha for this condition.
• Bipolar disorder. It is unclear if oral ashwagandha is beneficial for improving cognitive function in adults with bipolar disorder. Details: Clinical research shows that taking ashwagandha extract (Sensoril, Natreon, Inc.) 250 mg daily for 1 week and then 250 mg twice daily for 7 weeks, improves some, but not all, measures of cognition by a small-to-moderate amount when compared with placebo (90653).
• Bronchitis. Although there has been interest in using oral ashwagandha for bronchitis, there is insufficient reliable information about the clinical effects of ashwagandha for this condition.
• Cerebellar ataxia. It is unclear if oral ashwagandha is beneficial for improving balance in patients with cerebellar ataxia. Details: A small, open-label study evaluating ashwagandha 500 mg three times daily in combination with Ayurvedic therapy for one month showed improvement in balance indices in subjects with cerebellar ataxia when compared with baseline (19273). The validity of this finding is limited by the lack of a comparator group. Additionally, it is unclear if this effect is due to ashwagandha, other ingredients, or the combination.
• Chemotherapy-related fatigue. Evidence is limited to one small clinical study in patients with breast cancer. Details: In preliminary clinical research in patients with breast cancer, taking ashwagandha powdered root extract 2 grams (Himalaya Drug Co) three times daily through six cycles of chemotherapy decreases chemotherapy-related fatigue when compared with no treatment. Fatigue scores were 16% to 52% higher in the control group when compared to the ashwagandha group (90651).
• Chronic obstructive pulmonary disease (COPD). It is unclear if oral ashwagandha is beneficial in patients with COPD. Details: A small clinical study in patients with stable COPD shows that taking ashwagandha root extract 250 mg twice daily for 12 weeks, along with conventional therapy, improves measures of lung function and exercise tolerance, but not quality of life, when compared with conventional therapy alone (109588).
• Cognitive function. Although there has been interest in using oral ashwagandha for cognitive function, there is insufficient reliable information about the clinical effects of ashwagandha for this condition.
• Constipation. Oral ashwagandha has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A very small clinical study in adults with constipation shows that taking a combination product containing ashwagandha root and ambrette fruit extracts 300 mg or 500 mg daily for 14 days improves bowel movement frequency and abdominal, rectal, and stool symptoms when compared with placebo (112114). It is unclear if these effects are due to ashwagandha, ambrette, or the combination. The validity of these effects is limited by the small sample size.
• Coronavirus disease 2019 (COVID-19). Oral ashwagandha has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in adults hospitalized with COVID-19 shows that taking a specific combination product, (Artovid-20, Bioved Pharmaceuticals) containing ashwagandha, ginger, turmeric, and Boswellia, 1,776 mg orally twice daily for 14 days shortens the duration of symptoms by 0.9 days when compared with placebo. Taking the combination product also modestly reduced the severity ratings of some symptoms, such as sore throat and cough, however, these improvements are unlikely to be clinically relevant (109899). Another small clinical study in adults with mild to moderate COVID-19 shows that taking ashwagandha 500 mg and ginger 1000 mg twice daily for 15 days reduces time to recovery by around 6 days and increases the rate of clinical cure 14-fold and 2.6-fold at days 5 and 7, respectively, when compared with a control. However, taking this combination does not appear to improve the proportion of patients with a negative COVID-19 test, viral clearance, serum antibodies, chest findings, or disease progression when compared with control (112094). The validity of these findings is limited by a lack of blinding, and the study may have been inadequately powered to detect a difference between groups. Additionally, it is unclear if these effects are due to ashwagandha, ginger, or the combination.
• Diabetes. It is unclear if oral ashwagandha is beneficial for type 2 diabetes. Details: In patients with type 2 diabetes, preliminary clinical research shows that ashwagandha 3 grams daily for 30 days decreases blood glucose to a degree similar to oral hypoglycemic drugs (19274). However, this study did not compare ashwagandha directly to a group taking oral hypoglycemic drugs.
• Fibromyalgia. Although there has been interest in using oral ashwagandha for fibromyalgia, there is insufficient reliable information about the clinical effects of ashwagandha for this condition.
• Hiccups. Although there has been interest in using oral ashwagandha for hiccups, there is insufficient reliable information about the clinical effects of ashwagandha for this condition.
• Hypercholesterolemia. It is unclear if ashwagandha is beneficial for hypercholesterolemia. Details: A very small clinical study in subjects with hypercholesterolemia shows that ashwagandha 3 grams daily for 30 days decreases serum cholesterol, triglyceride, low-density lipoprotein (LDL) cholesterol, and very low-density lipoprotein (VLDL) cholesterol levels when compared with baseline (19274). The validity of these findings is limited by the lack of a comparator group.
• Hypothyroidism. It is unclear if ashwagandha is beneficial for hypothyroidism. Details: Preliminary clinical research in adults with subclinical hypothyroidism shows that taking a specific ashwagandha root extract (KSM-66, Ixoreal Biomed) 300 mg twice daily for 8 weeks increases triiodothyronine (T3) and thyroxine (T4) levels by 42% and 20%, respectively, and reduces serum TSH levels by 17% from baseline. These changes are significant when compared with placebo (97292). However, the effects of ashwagandha on thyroid hormone levels in patients with overt hypothyroidism, or in patients taking prescription thyroid hormones, is unknown.
• Infertility. Although there has been interest in using oral ashwagandha for infertility in females, there is insufficient reliable information about the clinical effects of ashwagandha for this condition.
• Male infertility. It is unclear if oral ashwagandha is beneficial for male infertility. Details: Preliminary clinical research in males with infertility shows that taking ashwagandha root powder for approximately 3 months modestly improves hormone levels, as well as sperm count and motility, when compared with baseline (19275,90650). The validity of these findings is limited by the lack of a comparator group. One study used a specific ashwagandha root extract (KSM-66 Ashwagandha, Ixoreal Biomed) 225 mg three times daily; another study provided doses of 5 grams daily (19275,90650).
• Menopausal symptoms. Oral ashwagandha may be beneficial for menopausal symptoms. Details: A small clinical study in healthy adults in perimenopause shows that taking a specific ashwagandha root extract (KSM-66, Ixoreal Biomed) 300 mg twice daily for 8 weeks improves menopausal symptom severity by 24%, compared with 11% in those receiving placebo. Quality of life and hot flashes also were improved in those taking ashwagandha (106785).
• Obsessive-compulsive disorder (OCD). It is unclear if ashwagandha is beneficial for OCD. Details: Preliminary clinical research shows that taking ashwagandha root extract 120 mg after meals for 6 weeks, in conjunction with prescribed selective-serotonin reuptake inhibitors (SSRIs), might reduce OCD symptom severity when compared with prescribed SSRIs alone. The dose was initiated at 30 mg daily and increased by 30 mg every 4 days. Although OCD scores were significantly reduced when compared with placebo, it should be noted that scores were already significantly lower in the placebo group at baseline (95618).
• Osteoarthritis. Oral ashwagandha has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: In patients with osteoarthritis, taking a specific combination supplement, containing ashwagandha 450 mg, Ayurvedic zinc complex 50 mg, guggul 100 mg, and turmeric 50 mg (Articulin-F) two capsules three times daily for 3 months reduces symptoms of pain and swelling when compared with placebo. However, there were no radiological improvements (19276). It is unclear if this effect is due to ashwagandha, other ingredients, or the combination.
• Parkinson disease. Oral ashwagandha has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: In patients with Parkinson disease, a small clinical study shows that taking a product containing ashwagandha 14.5 grams, cowhage 4.5 grams, Hyoscyamus reticulantus 0.75 grams, and Sida cordifolia 14.5 grams in lukewarm milk twice daily for 56 days improves symptoms like tremor, stiffness, and cramps when compared with baseline. The therapy followed 28 days of cleansing or eliminative therapy using Ayurvedic remedies (6899). The validity of these findings is limited by the lack of a comparator group. Also, it is unclear if these effects are due to ashwagandha, other ingredients, or the combination. Cowhage contains levodopa, which may contribute to any benefit seen with this combination product.
• Psychological well-being. It is unclear if oral ashwagandha is beneficial for improving psychological well-being in college students. Details: A small clinical study in healthy college students shows that taking ashwagandha root extract 350 mg twice daily for 30 days improves perceptions of well-being, including improvements in energy, mental clarity, food cravings, and sleep quality, when compared with placebo. Qualitative analysis also suggests these students had improvements in stress management, but stress scores were not reduced when compared with placebo (109589,109590).
• Rheumatoid arthritis (RA). It is unclear if ashwagandha is beneficial for improving symptoms of RA. Details: Preliminary clinical research shows that taking ashwagandha powder 5 grams twice daily for 3 weeks, followed by 4 weeks of sidh makardhwaj (a mixture of gold, mercury, and sulfur) 100 mg with honey daily, modestly improves symptoms in about 50% of males and 60% of females with RA when compared with baseline (95620). The lack of a control group limits the validity of this finding. Additionally, the effect of ashwagandha powder alone is unclear.
• Sexual dysfunction. Small clinical studies suggest that oral ashwagandha root extract may help improve sexual arousal and sexual desire in some females and males with sexual dysfunction. Details: Two, small clinical studies in adult females with sexual dysfunction show that taking ashwagandha root extract (KSM-66, Ixoreal Biomed) 300 mg twice daily with food for 8 weeks in conjunction with or without counseling increases the number of successful sexual encounters and improves orgasms, satisfaction, lubrication, and arousal when compared with placebo or counseling alone (95619,110492). Also, a small clinical study in adult males with low sexual desire shows that taking the same ashwagandha root extract 300 mg twice daily after meals for 8 weeks improves subjective sexual functioning scores, including measures of sexual arousal, sexual desire, sexual behavior, and orgasm, when compared with placebo (109586).
• Smoking cessation. Oral ashwagandha has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A moderate-sized clinical study in adults with a history of smoking 5 or more cigarettes daily for at least 3 years shows that taking a specific combination product containing ashwagandha 100 mg, Indian gooseberry, tribulus, bacopa, Albizia lebbeck, licorice, clove, ginger, cowhage, holy basil, and turmeric (Smotect, Smotect India) daily for 3 months reduces the number of cigarettes smoked daily and levels of alveolar carbon monoxide and carboxyhemoglobin but does not improve lung capacity when compared with placebo (112115). It is unclear if these effects are due to ashwagandha, other ingredients, or the combination.
• Tuberculosis. Although there has been interest in using oral ashwagandha for tuberculosis, there is insufficient reliable information about the clinical effects of ashwagandha for this condition.
• Vitiligo. Although there has been interest in using oral ashwagandha for vitiligo, there is insufficient reliable information about the clinical effects of ashwagandha for this condition.
• Wrinkled skin. It is unclear if topical ashwagandha is beneficial in individuals with wrinkled skin. Details: A small clinical study in healthy adults with photoaged skin shows that applying ashwagandha root extract 8% lotion daily for 60 days improves physician-rated scores for skin wrinkles, hydration, brightness, tone, and pigmentation and improves other measures of skin elasticity and hydration when compared with placebo. However, changes in melanin content did not differ between treatment groups (111538).
• Wound healing. Although there has been interest in using topical ashwagandha for healing of skin ulcers and skin sores, there is insufficient reliable information about the clinical effects of ashwagandha for this condition. More evidence is needed to rate ashwagandha for these uses.

(Read more about ASHWAGANDHA)

POSSIBLY EFFECTIVE

• Genital herpes. Oral eleuthero root extract might help to prevent and reduce the severity of genital herpes outbreaks. Details: One clinical study in patients with recurrent genital herpes infections shows that taking a specific eleuthero root extract (Elagen) 400 mg, standardized to contain eleutheroside 0.3%, daily for at least 3 months reduces the frequency, severity, and duration of outbreaks when compared with placebo (730).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Athletic performance. Small clinical studies suggest that oral eleuthero root is not beneficial for improving athletic performance. Details: One study in trained distance runners shows that a specific eleuthero root liquid extract, standardized to eleutherosides B and E content, taken as 3.4 mL daily for 6 weeks, does not affect endurance, performance, or psychological, cardiac, or respiratory parameters when compared with placebo (7522). Small studies in trained athletes or healthy adults show that taking eleuthero 800-1200 mg daily (Endurox) for 1-6 weeks does not seem to have any effect on cycling performance time, respiration, lactate production, or heart rate recovery during cycling, stair-stepping exercise, treadmill, or cyclic ergometry when compared with placebo (2335,7600,7601,8994). However, there has been some speculation that a longer duration of supplementation is needed for benefit. One study in recreationally trained athletes shows that taking a specific powdered eleuthero root product 400 mg twice daily for 8 weeks increased cycling endurance time by 23% and maximal oxygen consumption by 12% when compared with placebo. This product was standardized to contain eleutheroside B 0.11% and eleutheroside E 0.12% (17186).
• Bipolar disorder. It is unclear if oral eleuthero root is beneficial for bipolar disorder. Details: A small clinical study in Chinese adolescents ages 12-17 years with bipolar disorder shows that taking eleuthero root 750 mg orally three times daily, in conjunction with lithium for 6 weeks, induces similar response rates and remission rates when compared with lithium plus fluoxetine 20 mg (75028). It is not clear how this response rate compares to the use of lithium alone.
• Cardiovascular disease (CVD). It is unclear if oral eleuthero fruit is beneficial for preventing the development of CVD. Details: One small clinical study in healthy adults with at least two cardiovascular risk factors shows that taking an aqueous extract of eleuthero fruit 500 mg daily for 12 weeks seems to modestly reduce systolic blood pressure and arterial stiffness, as measured by brachial-ankle pulse wave velocity, when compared with placebo. It did not affect diastolic blood pressure, flow-mediated dilation, or carotid intima-media thickness. Also, taking a higher 1000 mg dose of the same eleuthero extract daily did not have significant effects on any measured parameters (105025).
• Chronic fatigue syndrome (CFS). It is unclear if oral eleuthero root is beneficial for CFS. Details: One clinical study in adults with CFS shows that taking eleuthero root extract 2 grams daily for 2 months improves fatigue severity and duration when compared with baseline, but not when compared with placebo (11099).
• Cognitive function. It is unclear if oral eleuthero is beneficial for cognitive function. Details: A very small clinical study in middle-aged people shows that taking eleuthero 325 mg twice daily might improve selective memory when compared with placebo (2574). Another very small study in healthy adults shows that taking a combination product containing extracts of eleuthero leaf 203 mg and Drynaria fortunei 20 mg daily for 12 weeks improves figure recall, but not immediate memory or attention, when compared with placebo (102316). It is unclear if this effect is due to eleuthero, Drynaria fortunei, or the combination.
• Common cold. Oral eleuthero has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Some clinical research shows that taking capsules of a specific combination product containing eleuthero plus andrographis (Kan Jang, Swedish Herbal Institute) orally improves symptoms of the common cold when started within 72 hours of symptom onset. Some symptoms can improve after 2 days of treatment; however, it typically takes 4-5 days of treatment for maximal symptom relief (5784,10795,12380). Some research shows the combination of eleuthero and andrographis relieves cold symptoms better than echinacea or placebo in children (12381). It is unclear if this effect is due to eleuthero, andrographis, or the combination.
• Diabetes. It is unclear if oral eleuthero is beneficial for improving glycemic control in type 2 diabetes. Details: One small clinical study in adults with type 2 diabetes shows that taking a specific eleuthero extract, standardized to contain eleutherosides E and B 1.12%, as 480 mg daily for 3 months, decreases fasting glucose by a mean of 36 mg/dL, postprandial blood glucose by a mean of 35 mg/dL, glycated hemoglobin (HbA1c) by a mean of 0.8%, triglycerides by a mean of 106 mg/dL, and total cholesterol by a mean of 21 mg/dL when compared with placebo (91509).
• Diabetic neuropathy. It is unclear if oral eleuthero is beneficial for diabetic neuropathy. Details: One small clinical study in adults with type 2 diabetes shows that taking a specific eleuthero extract, standardized to contain eleutherosides E and B 1.12%, as 480 mg daily for 3 months, modestly improves subjective symptoms of diabetic neuropathy when compared with placebo (91509).
• Familial Mediterranean fever. Oral eleuthero has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: One small clinical study in children ages 3-15 years with familial Mediterranean fever shows that taking a specific combination product (ImmunoGuard, Inspired Nutritionals) containing eleuthero, andrographis, schisandra, and licorice for one month reduces the duration, frequency, and severity of disease recurrence when compared with placebo (12382). It is unclear if this effect is due to eleuthero, other ingredients, or the combination.
• Fibromyalgia. Although there is interest in using oral eleuthero for fibromyalgia, there is insufficient reliable information about the clinical effects of eleuthero for this condition.
• Hangover. It is unclear if oral eleuthero root is beneficial for hangovers. Details: One small clinical study in healthy males shows that consuming one bottle of a powdered polysaccharide-rich extract of eleuthero root before and after consuming alcohol modestly reduces the severity of hangover as measured by the Acute Hangover Scale questionnaire score when compared with placebo (91508). However, the validity of these findings is brought into question due to the incomplete study information provided.
• Influenza. Oral eleuthero has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in adults with influenza shows that taking a specific combination product containing eleuthero 20-30 mg plus andrographis 178-266 mg (Kan Jang, Swedish Herbal Institute) three times daily for 3-5 days relieves symptoms more quickly than amantadine. This combination product also reduced the risk of post-influenza complications, such as sinusitis or bronchitis, when compared with amantadine (10441). It is unclear if these effects are due to eleuthero, andrographis, or the combination.
• Osteoarthritis. Oral eleuthero has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research shows that taking two capsules each containing 400 mg of a combination of eleuthero, Panax pseudoginseng, and rehmannia daily for 6 weeks improves physical function in individuals with knee osteoarthritis when compared with placebo. However, the combination does not seem to reduce pain or stiffness when compared with placebo (74950). It is unclear if this effect is due to eleuthero, other ingredients, or the combination.
• Osteoporosis. Oral eleuthero has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A very small clinical study in postmenopausal patients shows that taking low-dose calcium and vitamin D3 in combination with a 250 mg blend of rehmannia root and eleuthero stem bark extracts twice daily for 12 months attenuates the loss of spine and femur bone mineral density when compared with placebo or high-dose calcium and vitamin D (75036). It is unclear if this effect is due to eleuthero, rehmannia, or the combination.
• Pneumonia. Oral eleuthero has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in adults with acute, nonspecific pneumonia shows that taking a specific combination product (ADAPT-232), containing eleuthero, rhodiola, and schisandra, as 20 mL twice daily for 10-15 days in conjunction with conventional treatment, reduces the duration of antibiotic treatment and improves quality of life when compared with conventional treatment alone (71152).
• Quality of life. It is unclear if oral eleuthero root improves quality of life in older healthy adults. Details: A small clinical study in elderly volunteers shows that taking eleuthero 300 mg daily improves social functioning and mental well-being after 4 weeks of treatment when compared with placebo. However, this improvement was not maintained after 8 weeks of treatment (15586).
• Rheumatoid arthritis (RA). Although there is interest in using oral eleuthero for RA, there is insufficient reliable information about the clinical effects of eleuthero for this condition.
• Stress. It is unclear if oral eleuthero root is beneficial for stress. Details: One clinical study in adults 30-50 years of age with symptoms of stress shows that taking a specific eleuthero root extract (WS 1070) 120 mg daily for 8 weeks does not improve fatigue, exhaustion, cognitive alertness, or measures of stress when taken alone or in conjunction with stress management training (91510). However, another small clinical study in healthy females 20-68 years of age who have experienced stress for a prolonged period of time shows that taking a single, 270 mg dose of a combination agent (ADAPT-232) containing eleuthero, rhodiola, and schisandra improves attention and cognitive speed and accuracy when compared with placebo (19289). It is unclear if these effects are due to eleuthero, other ingredients, or the combination.
• Upper respiratory tract infection (URTI). Oral eleuthero has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research in adults with an uncomplicated URTI shows that taking 30 mL of a combination product (Kan Jang, Swedish Herbal Institute) containing extracts of eleuthero root (eleutherosides B and E 0.03 mg/mL), echinacea root, and malabar nut leaf daily does not reduce the severity or frequency of cough by a clinically meaningful amount after 3-4 days of treatment when compared with bromhexine hydrochloride or placebo (95648). However, a non-blinded clinical study shows that taking 30 mL of this same product three times daily for 6 days improves the severity and frequency of coughing and the degree of nasal congestion when compared with bromohexine. Additionally, patients taking the combination product recovered two days sooner, on average, than those taking bromohexine (48569). The reason for these conflicting findings is unclear but may be due to an inadequate duration of treatment in the first study and/or lack of blinding in the second study. Also, it is unclear if any benefit is due to eleuthero, other ingredients, or the combination. Other research has evaluated a capsule formulation of Kan Jang (Swedish Herbal Institute), with each capsule containing eleuthero root 11.4 mg and andrographis 195 mg. One small clinical study in patients with an uncomplicated URTI shows that taking this product as two capsules three times daily for 5 days reduces the median number of sick leave days to 2 days, compared with 3 days in the placebo group. It also increases the total number of recovered patients on day 3 to 75%, compared with 55% of those taking placebo (107471). More evidence is needed to rate eleuthero for these uses.

(Read more about ELEUTHERO)

POSSIBLY EFFECTIVE

• Anxiety. Orally, a specific lavender oil product (Silexan) seems to improve anxiety in some patients. Lavender oil aromatherapy and aromatherapy massage also seem to improve chronic and situational anxiety in some patients. Details: Most meta-analyses and clinical trials in patients with mild to severe anxiety show that taking capsules containing a specific lavender oil ingredient (Silexan, Dr Willmar Schwabe GmbH & Co. KG) 80-160 mg orally daily for 6-10 weeks improves anxiety when compared with placebo. However, heterogeneity and small sample sizes limit the validity of these findings (58077,58080,58098,95640,103061,103069). A meta-analysis of a subgroup of these clinical studies shows that taking Silexan 80 mg orally once daily for 10 weeks also reduces anxiety in patients with subthreshold anxiety disorders, which meet some but not all criteria for generalized anxiety disorder (97257). Limited research compares Silexan to the conventional medications paroxetine and lorazepam. One clinical study shows that taking Silexan 80 mg daily for 6 weeks improves anxiety and quality of sleep similarly to low-dose lorazepam (Ativan) 0.5 mg in adults with generalized anxiety disorder (58077). Another clinical study in adults with generalized anxiety disorder shows that taking Silexan 80-160 mg daily for 10 weeks reduces symptom severity similar to paroxetine 20 mg daily (93004). A network meta-analysis suggests that the higher dose of Silexan (160 mg) might be more effective when compared with paroxetine 20 mg or lorazepam 0.5 mg (103069). Limited research has assessed other oral formulations of lavender. A small clinical study in postmenopausal adults with mild to moderate anxiety shows that taking a dried lavender flower powder 500 mg twice daily for 8 weeks reduces anxiety by about 6% when compared with placebo, as measured on the State-Trait Anxiety Inventory Scale (97256). The clinical significance of this improvement is not clear. Meta-analyses of clinical trials in patients with chronic or situational anxiety show that inhalation aromatherapy or aromatherapy massage using lavender oil moderately reduces anxiety when compared with control. Most often, the control group received no intervention although occasionally they received standard or routine care. In some studies, plain water or diluted lemon juice were used as controls. Most treatments with lavender aromatherapy were given as single sessions of 1-30 minutes. However, occasionally multiple sessions were used (101720,103061,109974). Most other individual clinical trials of aromatherapy with lavender, alone or in combination with bergamot, are in agreement with these findings (58103,95637,97258,99713,101722,101724,108752,109854,109981), although some research does not support the use of lavender aromatherapy for anxiety (29504,58053,97258,101724,109853). The poor quality of most of the available research makes it difficult to determine which patients, if any, are most likely to benefit.
• Depression. Oral lavender, in the form of tea, tincture, powder, or a specific oil (Silexan), seems to reduce depressive symptoms in some patients. Early research also shows that lavender oil aromatherapy seems to improve symptoms of depression. Details: When used orally, lavender may be beneficial in some patients with depression. A meta-analysis of five clinical trials shows that oral lavender is moderately more beneficial than a control group for reducing symptoms of depression (109860). Most studies included in the analysis were low- to moderate-quality with variation in patient demographics. Studies in the analysis investigated the effects of oral lavender oil or powder in menopausal or postpartum patients, or in patients with major depression, and compared lavender with routine care, placebo, medication, or no intervention. Doses have included powdered lavender leaves 1-2 grams daily for 8 weeks, lavender tea made from 2 grams powder per teabag once or twice daily for 2 weeks, and a specific oral capsule containing lavender oil (Silexan, Dr. Willmar Schwabe GmbH & Co. KG) 80 mg daily for 70 days (103060,104433,109860). Other preliminary clinical research in patients with depressed mood shows that taking Silexan 80 mg daily for 6 weeks can improve depression scores by about 33% when compared to baseline (58098). Also, a small clinical study in patients with mild to moderate depression shows that drinking a tincture of lavender appears to be slightly less effective than imipramine; however, lavender might have some additive antidepressant effects when used in combination with imipramine (9792). The validity of these findings is limited by the lack of a placebo group and small study size. Lavender has also been taken in combination with other products. A small clinical study in patients with depression and anxious distress shows that taking 5 mL of a syrup containing lavender flower extract and Chinese dodder extract twice daily for 6 weeks seems to reduce depression to a similar degree as citalopram 20 mg daily (104437). It is unclear if the benefit is due to lavender, Chinese dodder, or the combination. Lavender oil aromatherapy has also been evaluated. A meta-analysis of nine clinical trials shows that lavender oil aromatherapy is moderately more beneficial than control for reducing symptoms of depression. Most studies included in the analysis were low- to moderate-quality with variation in patient demographics. Studies in the analysis investigated the effects of lavender oil aromatherapy in a variety of patient populations, and no studies were specific to patients with depression. Lavender aromatherapy was compared with no intervention, routine care, other aromatherapy oils, or distilled water (109860). However, in hospitalized patients undergoing microvascular breast reconstruction, lavender oil aromatherapy does not improve symptoms of perioperative depression when compared with coconut oil (109853). Lavender oil has also been studied in combination with other oils as aromatherapy. A small clinical study in community-dwelling older adults shows that inhalation or massage with lavender, sweet orange, and bergamot oils twice weekly for 8 weeks improves depressive symptoms in 55% to 65% of patients when compared with a control (98474). Another small clinical study in postmenopausal adults shows that a combination of aromatherapy with lavender and bergamot oils three times daily for 8 weeks along with routine care modestly improves symptoms of depression when compared with routine care alone (109981). It is unclear if any benefit is due to lavender, other ingredients, or the combination.
• Dysmenorrhea. Limited clinical research suggests that lavender oil aromatherapy might reduce dysmenorrhea symptoms. Details: A clinical study in young adults with dysmenorrhea shows that applying 3 drops of lavender oil to a piece of cotton and inhaling for 30 minutes daily for the first 3 days of menstruation modestly reduces pain when compared to inhaling the scent of diluted milk (95635). Another small clinical study in patients with dysmenorrhea shows that applying 3 drops of lavender oil to the hands and inhaling for 5 minutes every 6 hours for the first 3 days of menstruation seems to reduce abdominal pain and backache when compared with inhaling the scent of sesame oil (90510). Lavender oil has also been added to abdominal massage. A clinical crossover study in young females with dysmenorrhea shows that administering a gentle abdominal massage with lavender essential oil for 15 minutes moderately reduces pain immediately after treatment when compared with a massage with petrolatum (58106). It is unclear if the benefit persists after the end of the treatment. Additionally, because all available research has been conducted in the Middle East, it is unclear if these results can be extrapolated to other geographic locations.

POSSIBLY INEFFECTIVE

• Cancer-related pain. Using lavender oil for massage or as an aromatherapy diffusion does not seem to provide any additional pain relief in patients with advanced or terminal cancer. Details: Clinical research in patients with advanced or terminal cancer shows that diffusing lavender oil as aromatherapy or using lavender oil for massage does not improve pain scores when compared with control treatments without lavender oil (29504,58053).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Alopecia areata. Topical lavender oil has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in patients with alopecia areata shows that applying lavender oil in combination with essential oils from thyme, rosemary, and cedarwood daily for 7 months seems to improve hair growth in 44% of participants when compared with 15% of those using only carrier oils (5177). It is unclear if this effect is due to lavender oil, other oils, or the combination.
• Atopic dermatitis (eczema). Although there is interest in using topical lavender oil for eczema, there is insufficient reliable information about the clinical effects of lavender oil for this condition.
• Burns. It is unclear whether lavender oil aromatherapy is beneficial as adjunct treatment for reducing pain associated with dressing changes in children with burns. Details: Preliminary clinical research in young children with second-degree burns shows that lavender oil aromatherapy, provided as 0.5 mL dripped onto a gauze pad and placed 20 cm away from the child's nose for 15 minutes before a dressing change, modestly reduces pain severity at 1 and 30 minutes after the dressing change when compared with placebo aromatherapy with jojoba oil. Use of lavender oil aromatherapy also attenuated increases in heart and respiratory rates after the dressing change (109857).
• Canker sores. Topical lavender oil might improve canker sore healing and reduce swelling and pain. Details: A clinical study shows that applying 2 drops of lavender oil to canker sores three times daily might reduce redness, swelling, and pain when compared with placebo (58099).
• Colic. It is unclear whether lavender oil aromatherapy massage is beneficial for reducing colic symptoms in infants. Details: A small clinical trial shows that using lavender oil diluted with almond oil to massage the belly of infants for 5-15 minutes beginning at the onset of colic reduces average weekly crying times by about 7 hours when compared with infants not receiving aromatherapy massages (58096). It is unclear if this effect is due to lavender oil, massage, or the combination.
• Coronary artery bypass graft (CABG) surgery. Small clinical studies suggest that lavender aromatherapy might modestly improve sleep and reduce pain in patients who have undergone CABG surgery. Details: One small clinical study shows that placing three drops of lavender oil (Barich Essence Company) on the pillow every night for 5 nights modestly improves sleep quality, but not sleep latency, duration, or efficiency, when compared with placebo (109861). Another small clinical study shows that placing 2 drops of lavender oil on a cotton ball for overnight aromatherapy starting on the second evening after surgery modestly improves sleep quality on the second and third nights of use, but not the first night, when compared with distilled water (109856). Also, a small clinical study shows that applying 5 drops of lavender oil 20% to a gauze which is worn around the neck for 30 minutes after CABG surgery modestly reduces postoperative pain on the day of surgery and the day after surgery when compared with pre-aromatherapy pain levels. These changes were greater than those seen in patients inhaling distilled water (109850). However, one small clinical study shows that inhaling 2 drops of lavender oil 2% for 20 minutes on postoperative days 2 and 3 does not reduce mental stress when compared with placebo (93009).
• Coronavirus disease 2019 (COVID-19). It is unclear if oral lavender is beneficial for olfactory dysfunction in patients with COVID-19. Details: A small preliminary clinical trial in patients with olfactory dysfunction related to COVID-19 shows that taking lavender syrup 9 mL twice daily for 3 weeks in combination with routine treatments modestly reduces symptoms when compared with routine treatments alone. However, there was no change in symptom scores or the percentage of patients with complete improvement in olfactory or taste dysfunction. The lavender syrup was made by preparing a water extract of the dried aerial parts and mixing with honey and water (109864).
• Dementia. Small clinical studies suggest that diffused aromatherapy with lavender oil may modestly improve agitation symptoms in patients with dementia; however, lavender oil applied to the patient or the patient's clothes might not be beneficial. Details: Some small and heterogeneous clinical studies in patients with dementia show that applying lavender oil aromatherapy via a diffuser for either 20 minutes twice daily, 2 hours daily, or once nightly for up to 3 weeks seems to improve agitation when compared with baseline, water, or a sunflower oil placebo (16393,58052,95632). However, using aromatherapy that is applied to the person's clothes or arms does not seem to help. Small clinical studies in patients with moderate or advanced dementia show that applying lavender oil to a pad attached to a patient's shirt does not reduce agitation when compared with placebo (12213,99710). Another clinical study in nursing home residents with dementia and frequent agitated behavior shows that applying 1 mL of 30% lavender oil to each forearm does not reduce agitation or improve mood when compared with applying placebo oil (93014).
• Diabetic neuropathy. It is unclear if lavender aromatherapy massage is beneficial for diabetic neuropathy. Details: Preliminary clinical research in patients with neuropathic pain related to diabetes shows that a gentle foot massage with lavender essential oil 3% in sunflower oil for 10 minutes nightly for 1 month reduces neuropathic pain and improves quality of life when compared with a placebo sunflower oil massage or routine care alone (109858).
• Fall prevention. It is unclear if lavender aromatherapy prevents falls in elderly patients. Details: A clinical study in nursing home residents aged 65 years or older shows that attaching a patch with lavender oil (Aromaseal Lavender, Hakujuji Co.) onto the neckline of clothing once daily for one year seems to have a non-significant trend toward reduced fall incidence when compared with placebo (58101).
• Fatigue. Small clinical studies suggest that lavender aromatherapy may modestly reduce fatigue in patients with underlying medical conditions, such as kidney failure or heart disease. The effects of lavender for fatigue in otherwise healthy adults is unclear. Details: Most small clinical studies in adults with kidney failure show that receiving aromatherapy with lavender essential oil during hemodialysis sessions for 4 weeks reduces fatigue when compared with baseline, a control group, or a placebo group (98524,109867). However, one small clinical study in these patients shows that applying lavender oil for inhalation for 10 minutes during dialysis sessions for 4 weeks does not reduce fatigue when compared with control (95642). Lavender aromatherapy has also been tried in patients hospitalized with various forms of cardiac disease. A small clinical trial shows that placing 3 drops of lavender oil on a cotton ball and inhaling for 20 minutes nightly for 7 days improves fatigue scores by 21 points, compared with a 2-point improvement in those receiving placebo (107959). The validity of these findings is limited due to the short duration of treatment.
• Hypertension. Although there is interest in using lavender aromatherapy for hypertension, there is insufficient reliable information about the clinical effects of lavender for this condition.
• Insect repellent. Although there is interest in using topical lavender to repel insects, there is insufficient reliable information about the clinical effects of lavender for this condition.
• Insomnia. Inhalation aromatherapy or aromatherapy massage with lavender oil may improve some subjective measures of sleep, but results are conflicting and improvements appear minimal at best. Additionally, most small clinical studies suggest it does not improve sleep in hospitalized patients. Details: Lavender oil aromatherapy seems to improve sleep quality in some patients, although it is unclear which patient populations may be most likely to be benefit. A clinical study in healthy college students with self-reported sleep problems shows that wearing a patch containing lavender oil 55 mcL on the chest, in addition to practicing sleep hygiene, improves self-reported sleep quality, but not sleep quantity, when compared with wearing a placebo patch (93012). Another small clinical study in elderly patients that have trouble sleeping in nursing homes shows that placing 2 drops of lavender oil to a cotton pad on a nightstand at bedtime for 4 weeks moderately improves sleep quality and reduces fatigue when compared with control (103062). A meta-analysis of three clinical trials shows that lavender modestly improves postpartum sleep quality when compared with control, including placebo or no intervention. However, each trial used a different form of lavender, including a topical cream, a tea, and aromatherapy. Also, the individual trials included in the analysis show that only the cream and aromatherapy resulted in statistically significant improvements in sleep quality (109866). Conversely, a small clinical study in postmenopausal adults with insomnia who received sleep hygiene guidance shows that inhaling lavender oil 6% before bed nightly for 1 month does not improve sleep quality when compared with sunflower oil. The oil was inhaled from the bottle for two, two-minute sessions and then poured on a cotton ball and placed near the head while sleeping (109852). Lavender aromatherapy has also been evaluated for insomnia in patients with comorbid disease states. A clinical study in patients with insomnia and type 2 diabetes shows that lavender oil aromatherapy for 5 minutes at bedtime nightly for 4 weeks improves sleep when compared with almond oil (103065). Preliminary clinical research in adults with kidney failure shows that foot massage with lavender oil 1.5% for 3 weeks during hemodialysis modestly improves sleep quality when compared with routine care, but is no more effective than sweet orange oil (109859). Another preliminary clinical study in cancer patients shows that receiving aromatherapy as two drops of pure lavender oil applied to a cotton ball and attached to the collar for 20 minutes at bedtime for one week improves sleep when compared with baseline, but seems to be no better than using peppermint oil or a lavender oil 1% control (103063). The validity of this finding is limited because the lavender oil 1% control resulted in notable benefit and might have been an inadequate control treatment. Aromatherapy with lavender oil does not seem to improve sleep in most hospitalized patients, including patients in intermediate care units, hospitalized cardiac patients, and in patients undergoing microvascular breast reconstruction. Aromatherapy treatments have included lavender aromatherapy throughout hospitalization, placing 3 mL of lavender oil 3 feet away from the bed during sleep, and hand and lower leg massage with lavender essential oil 1.5% in sweet almond oil at bedtime (93013,101727,109853). However, studies have generally been small and did not use proper controls. Also, some small clinical studies suggest that lavender aromatherapy might have modest beneficial effects in patients undergoing coronary artery bypass graft (CABG) surgery (109856,109861).
• Kidney failure. Small clinical studies suggest that lavender aromatherapy may modestly reduce fatigue and improve sleep quality in adults receiving hemodialysis. Lavender oil massage may also modestly improve symptoms of restless leg syndrome (RLS) in these patients. Details: Multiple small studies have evaluated lavender aromatherapy, provided during hemodialysis sessions, for reducing fatigue. A small clinical study shows that applying 5% lavender essential oil (Barij Essence Pharmaceutical Company) to a cotton ball on the patient's collar for inhalation for 15-20 minutes twice daily during each session for 1 month reduces fatigue by an additional 44% and 40% when compared with baseline and control, respectively (98524). Another preliminary clinical trial shows that applying lavender oil 7% in sweet almond oil to a gauze pad placed 20 cm from the patient's nose for 2 minutes improves fatigue when compared with placebo aromatherapy. By the third week of four total weeks of treatment, most patients given lavender oil aromatherapy had only mild fatigue, compared with moderate or severe fatigue in the control group (109867). Also, a small clinical trial shows that aromatherapy or aromatherapy foot massage with lavender and sweet orange oil for 10-20 minutes during each session for 2 months reduces fatigue when compared with no treatment. Aromatherapy massage seems to be more effective than aromatherapy alone (103068). However, one small clinical study shows that applying the oil for inhalation for 10 minutes during each session for 1 month does not reduce fatigue when compared with control (95642). The difference in these findings might be due to study size, lavender oil concentration, or the frequency and duration of aromatherapy sessions. Lavender aromatherapy has also been evaluated for reducing insomnia in adults on hemodialysis. A small clinical study shows that foot massage with lavender oil 1.5% for 3 weeks during hemodialysis sessions modestly improves sleep quality when compared with routine care. However, it does not seem to be more effective than using sweet orange oil (109859). Some small clinical studies in patients undergoing hemodialysis show that massaging the feet or lower legs with lavender oil reduces the severity of RLS by up to 45% when compared with routine care, massage only, or baby oil as placebo (95638,103064,109865). However, massage with lavender oil does not seem to be more beneficial than glycerin oil 2% or sweet orange oil 1.5% for reducing RLS severity (103064,109859). Doses have included 10-15 mL of 1.5% or 5% lavender oil for 10- to 45-minutes during hemodialysis sessions for 3-4 weeks (95638,103064,109859,109865).
• Labor pain. Lavender aromatherapy may help to reduce pain during childbirth. Details: A meta-analysis of clinical trials in pregnant patients in Iran shows that lavender oil aromatherapy applied by various means, such as mask or massage, reduces labor pain when compared with control (104440). All available research has been conducted in Iran, so it is unclear if the benefit can be extrapolated to other geographic locations.
• Lice. Topical lavender oil has only been evaluated in combination with other essential oils; its effect when used alone is unclear. Details: Clinical studies in patients with head lice shows that applying lavender oil in combination with tea tree oil reduces the number of hatched and unhatched live lice when compared with control (19188,19189). When applied with tea tree oil three times weekly, lavender oils seems to improve lice eradication when compared with two weekly treatments of pyrethrin and piperonyl butoxide (19189). It is not known if these effects are due to tea tree oil, lavender, or the combination.
• Menopausal symptoms. It is unclear if lavender aromatherapy reduces menopausal symptoms such as hot flushes. Details: A meta-analysis and individual clinical studies in postmenopausal adults show that lavender aromatherapy for 4-12 weeks, alone or in combination with other essential oils, reduces menopausal symptoms such as hot flushes when compared with placebo (95634,99711,103067). However, heterogeneity and small sample sizes limit the validity of these findings. A small clinical study in postmenopausal adults shows that aromatherapy with lavender 2% oil for 20 minutes at bedtime every day for 1 month improves quality of life scores when compared to baseline (99711). Another small clinical study in menopausal adults shows that receiving aromatherapy with lavender oil and lemon oil for 5 minutes daily for 30 days seems to improve sleep and quality of life when compared with placebo (104439). However, a small clinical study in postmenopausal adults shows that a combination of lavender and bergamot oils administered via inhalation three times daily for 8 weeks with routine care does not improve sexual function when compared with routine care alone (109981).
• Migraine headache. It is unclear if lavender aromatherapy improves migraine symptoms. Details: A small clinical study in patients with migraine headaches shows that rubbing 2-3 drops of lavender oil on the upper lip for inhalation might reduce headache pain and associated symptoms such as nausea and photophobia. Of 129 headaches treated with lavender oil, 92 responded completely or partially, compared with 32 of 68 headaches in the placebo group (18209).
• Multiple sclerosis (MS). It is unclear if lavender aromatherapy can improve memory in patients with MS. Details: A small preliminary clinical trial in patients with MS shows that dripping 2 drops of lavender oil (Barij Essence Pharmaceutical Company) on a cotton ball for inhalation for 10 minutes twice daily for 2 weeks improves working memory by a small amount when compared with inhaling distilled water (109855).
• Multiple sclerosis-related fatigue. It is unclear if oral lavender is beneficial for reducing fatigue in adults with multiple sclerosis (MS). Details: A small clinical trial in patients with MS shows that taking lavender 600 mg three times daily for 60 days improves fatigue by a large amount when compared with placebo (109851).
• Neuropathic pain. Although there is interest in using topical lavender oil for neuropathic pain, there is insufficient reliable information about the clinical effects of lavender for this condition.
• Osteoarthritis. It is unclear if lavender aromatherapy with massage reduces osteoarthritis pain. Details: A small clinical study in patients with osteoarthritis shows that applying 5 mL of 3% lavender oil (Barij Essence Pharmaceutical Company) to the knee through self-administered massage three times weekly for 3 weeks can reduce pain by 23% when compared to massage with placebo oil and by 36% when compared with no treatment. However, any benefits of treatment begin to wear off after treatment completion (95645).
• Otitis media. Topical lavender oil has only been evaluated in combination with other essential oils; its effect when used alone is unclear. Details: A clinical study in children ages 5-18 years with otitis media and otalgia shows that administering ear drops containing lavender and other herbal extracts, alone or in combination with a topical anesthetic, improves ear pain when compared with baseline. However, it is possible that the pain is self-limited and any pain reduction is due to natural resolution (39500).
• Pain (acute). Small clinical studies suggest that lavender aromatherapy may modestly reduce acute pain from needle insertion or other procedures in infants and adults. Details: Two small clinical studies in patients having a needle inserted for hemodialysis shows that inhaling 10% lavender essence for 5 minutes or topically applying 0.3 mL of 100% lavender oil for 5 minutes prior to needle insertion modestly reduces pain when compared with using placebo oil or water (93008,93010). Lavender aromatherapy has also been tried for gynecological exam pain. A clinical study shows that inhaling 10% lavender oil from a heat lamp for 10-15 minutes prior to gynecological exams can reduce pain experienced during the exam up to three-fold when compared to those receiving no treatment (95639). Lavender oil aromatherapy may also reduce vaccination, needle stick, and heel-lancing pain in infants. One clinical study shows that inhaling the scent of lavender oil (Barij Essence Pharmaceutical Company) 0.5% drops for one minute before vaccination modestly reduces pain and decreases crying time by about 20 seconds when compared with sweet almond oil (109869). A small clinical study in term infants shows that being placed in an incubator with lavender essential oil scent overnight before receiving a blood draw modestly reduces overall pain scores when compared with no intervention, but seems to be no different than giving 2 mL of 30% glucose solution (103066). Another small clinical study in premature infants shows that inhaling the scent of 6 lavender oil drops on a cotton ball for 3 minutes before and 30 seconds after a heel-lancing procedure seems to reduce pain scores when compared with exposure to an unscented cotton ball (104442). Lavender oil aromatherapy may also reduce pain due to frenotomy in infants. Preliminary clinical research shows that applying a gauze pad containing one drop of lavender oil under the nose, starting 2 minutes before the frenotomy and continuing throughout the procedure, modestly reduces pain when compared with routine care, which includes swaddling, oral sucrose, and pre-frenotomy sucking. Post-frenotomy crying was also reduced by about 50%, or 10 seconds (109868). Lavender oil seems to be similarly effective to vanilla oil (109810).
• Postdural puncture headache. It is unclear if lavender aromatherapy improves postdural puncture headache severity. Details: A small clinical study in patients with postdural puncture headache shows that receiving lavender oil aromatherapy for 15 minutes modestly improves pain immediately after treatment when compared with placebo. However, the pain relief is not maintained at 30 minutes after treatment (104441).
• Postoperative nausea and vomiting (PONV). It is unclear if lavender aromatherapy reduces PONV. Details: A small clinical study in postoperative patients shows that inhaling the scent of 2 drops of lavender oil from a cotton pad for 5 minutes improves nausea scores in 83% of people, compared with 44% of those inhaling a placebo. There was no difference in vomiting scores between groups (99712). Another small clinical study in patients after percutaneous nephrolithotomy shows that inhaling the scent of 3 drops of lavender essential oil from a gauze for 5 minutes immediately after the operation, and again 3 and 6 hours later, does not improve nausea or vomiting when compared with a control group that was not receiving aromatherapy (103872).
• Postoperative pain. The evidence for the use of lavender aromatherapy for pain after various types of surgical procedures is preliminary and conflicting. Details: Some preliminary clinical research in patients post-Cesarean section shows that, when used in conjunction with standard analgesic therapy, applying 2 drops of lavender oil 2% to a face mask or applying 3 drops of lavender to a cotton ball for inhalation seems to reduce postoperative pain when compared with control (58093,101724). Additionally, preliminary clinical research in patients undergoing coronary artery bypass graft (CABG) surgery shows that applying lavender oil to a gauze which is worn around the neck may modestly reduce postoperative pain on the day of surgery and the day after surgery when compared with distilled water (109850). Also, a small clinical study in children aged 6-12 years post-tonsillectomy shows that rubbing lavender oil onto the palms and inhaling for 3 minutes every 6 hours as needed reduces the use of acetaminophen when compared with control (90513). However, aromatherapy with lavender throughout hospitalization does not seem to improve postoperative pain in patients undergoing microvascular breast reconstruction when compared with coconut oil (109853).
• Postpartum complications. It is unclear if topical or inhaled lavender reduces postpartum complications such as pain and swelling. Details: Some clinical research in patients receiving an episiotomy during childbirth shows that adding lavender oil to water or sitz baths for up to 10 days might reduce episiotomy redness and discomfort when compared with using no lavender and standard treatment, such as povidone-iodine. However, findings are mixed as to whether adding lavender oil to baths helps to reduce edema and analgesic use (58085,58092,58116,58121). Lavender aromatherapy has also been studied to improve wellbeing in postpartum patients. A small clinical study in postpartum patients immediately following a natural birth shows that inhaling lavender oil from a cotton ball for 10-15 minutes in the morning, 6 hours later, and at bedtime, improves perceived pain, fatigue, distress, and mood within 1 hour of treatment and also the next morning when compared with placebo (95631).
• Postpartum depression. Small clinical studies suggest that aromatherapy with lavender oil may modestly improve or prevent depressive symptoms in postpartum patients. Details: A clinical study in healthy postpartum patients shows that placing 3 drops of lavender essential oil on the palms three times daily for 4 weeks after delivery moderately reduces depressive symptoms and anxiety when compared with usual care only (95637). There is limited research on the benefits of lavender aromatherapy in patients diagnosed with postpartum depression. A small clinical trial in these patients shows that a combination of lavender and rose essential oils, administered via inhalation or aromatherapy massage using hand "M" technique for 15-minute sessions, twice weekly for 4 weeks, reduces depression scores when compared with no intervention (58103).
• Pre-procedural anxiety. It is unclear if lavender aromatherapy can reduce preoperative or preprocedural anxiety; results from clinical research are generally of low-quality and benefits are modest at best. Details: A meta-analysis of four small clinical studies in patients undergoing cardiac surgery shows that lavender aromatherapy modestly reduces preoperative anxiety when compared with control (103058). However, the included studies were conducted in the Middle East, and it is unknown if these results are generalizable to other geographic areas. There is conflicting clinical evidence regarding the effect of lavender aromatherapy on anxiety prior to a dental procedure (58078,101725,103059). Small clinical studies also show mixed results as to whether lavender oil aromatherapy applied to a gauze bandage or oxygen mask improves anxiety in patients waiting for breast surgery when compared with usual care. (95641,101729). Lavender aromatherapy might reduce anxiety prior to less risky and extensive procedures such as needle injections. Small clinical studies in adults receiving botulinum toxin type A injections or children receiving dental injections show that lavender oil aromatherapy reduces heart rate and cortisol levels when compared with placebo (58089,104438). Another clinical study in preoperative patients undergoing insertion of a peripheral venous cannula shows that inhalation of 1% lavender oil (Talya Herbal Products) from a gauze pad for 5 minutes modestly reduces pain and anxiety scores and improves patient satisfaction when compared with control (95636). However, a clinical study in patients undergoing a colonoscopy or esophagogastroduodenoscopy shows that inhaling lavender oil does not reduce anxiety, although it does improve patient satisfaction, when compared with placebo (58066). Reasons for conflicting findings are unclear but may relate to the severity of anxiety, the specific outcomes measured, and cultural differences occurring in different geographic locations.
• Psychological well-being. It is unclear if topical or inhaled lavender improves well-being. Details: A small clinical study in healthy females shows that adding 3 mL of a mixture containing 20% lavender oil and 80% grapeseed oil to daily baths modestly improves mood when compared with baths containing grapeseed oil alone (15534). However, lavender may not impact well-being in patients with cancer. Clinical research shows that that adding lavender oil for an aromatherapy massage in patients with advanced or terminal cancer does not improve well-being or quality of life when compared with no massage treatment or massage with inert oil (29504,58053).
• Restless legs syndrome (RLS). Most preliminary clinical research suggests that lavender oil aromatherapy massage is beneficial for RLS in patients undergoing hemodialysis. Its effect in other patient populations is unclear. Details: Some small clinical studies in patients undergoing hemodialysis show that massaging the feet or lower legs with lavender oil reduces the severity of RLS by up to 45% when compared with routine care, massage only, or baby oil as placebo (95638,103064,109865). However, massage with lavender oil does not seem to be more beneficial than glycerin oil 2% or sweet orange oil 1.5% for reducing RLS severity (103064,109859). Doses have included 10-15 mL of 1.5% or 5% lavender oil for 10 to 45 minutes during hemodialysis sessions for 3-4 weeks (95638,103064,109859,109865).
• Stress. Small studies suggest that inhaled lavender oil does not reduce stress in students under academic stress. Details: A meta-analysis of 21 moderate- to high-quality, small- to medium-sized studies shows that inhaling lavender oil modestly reduces stress when compared with control. Most studies included in the analysis have used lavender oil as aromatherapy; other studies have used a cream (109863). Also, inhaling lavender oil 3% in almond oil twice daily for 30 minutes during the exam period does not reduce academic stress or associated symptoms, including headache, blood pressure, or heart rate, in pharmacy students when compared with inhaling an odorless oil, although both were more effective than no intervention (101723).
• Toothache. Although there is interest in using topical lavender oil for toothache, there is insufficient reliable information about the clinical effects of lavender oil for this purpose. More evidence is needed to rate lavender for these uses.

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INSUFFICIENT RELIABLE EVIDENCE to RATE

• Altitude sickness. It is unclear if oral rhodiola is beneficial for altitude sickness. Details: Preliminary clinical research shows that taking rhodiola 447 mg four times daily for 7 days does not improve blood oxygenation or markers of oxidative stress when compared with placebo in subjects exposed to simulated high-altitude conditions (25402).
• Anthracycline cardiotoxicity. It is unclear if oral rhodiola is beneficial for epirubicin-induced cardiotoxicity. Details: Preliminary clinical research in breast cancer patients shows that taking salidroside, a constituent of rhodiola, 600 mg daily, beginning one week prior to chemotherapy and continuing throughout chemotherapy administration, reduces epirubicin-induced early left ventricular regional systolic dysfunction when compared with placebo (90434).
• Anxiety. It is unclear if oral rhodiola is beneficial for anxiety. Details: Preliminary clinical research in college students with anxiety shows that taking a specific dried rhodiola extract (Vitango, Schwabe Pharma) 200 mg twice daily for 14 days modestly reduces reported levels of anxiety, anger, confusion, negative mood, and stress when compared with a control group. However, rhodiola extract does not seem to improve cognition (96462).
• Arrhythmia. Although there has been interest in using oral rhodiola for arrhythmia, there is insufficient reliable information about the clinical effects of rhodiola for this condition.
• Athletic performance. The evidence related to the use of rhodiola for athletic performance is mixed, although specific standardized extracts might be beneficial for certain performance endpoints. Details: The available evidence for rhodiola in athletic performance includes small clinical trials in recreationally active or trained athletes. Trials using rhodiola extracts standardized to 3% rosavins and 1% salidroside (eg. Finzelberg, GmbH) show that taking 3 mg/kg, 200 mg, or 500 mg prior to exercise testing, either as a single dose or with a 3-day lead-in dose, modestly improves performance endpoints on a cycle ergometer. Improved endpoints included time to exhaustion, peak oxygen use, time to completion, perceived exhaustion, anaerobic capacity, and power (13109,90432,100168). However, in trials in which rhodiola was not taken the morning of testing, or when performance endpoints included forearm endurance or marathon time and recovery, rhodiola 170 mg to 1500 mg daily did not affect perceived exertion, time to exhaustion, or peak oxygen use (15574,19284,90433). A small crossover trial shows that taking 500 mg of rhodiola extract, standardized to 3% rosavins and 1% salidroside, three times daily for 3 days followed by 500 mg 30-minutes before exercise testing increases bench press velocity but decreases bench press repetition volume when compared with placebo (110543). Furthermore, limited evidence suggests that rhodiola extract does not affect muscle strength, speed of limb movement, reaction times, or attention span (13109) but might reduce plasma creatine kinase levels (19284). Also, while some evidence suggests that rhodiola extract can reduce blood lactate levels (19284), other research shows that it increases blood lactate levels after resistance training to a greater degree than placebo (110543). In general, it appears that acute doses of rhodiola may improve specific physical performance parameters, but neither acute nor chronic doses appear to notably improve muscle function. Some research has also assessed rhodiola when used in combination with other ingredients. A small clinical study in trained male cyclists shows that taking a specific combination product (Optygen, First Endurance) containing rhodiola 600 mg (standardized to 3% rosavin and 2.5% salidroside) plus cordyceps 2000 mg (standardized to 7% cordycepic acid), daily for 6 days followed by a half-dose daily for 7 days does not improve time to exhaustion or muscle tissue oxygen saturation when compared with placebo (15573). Additionally, a small crossover study in healthy, recreationally active adult males shows that taking a 30:70 blend of rhodiola and maral root extracts at a dose of 350 mg or 175 mg, ninety minutes prior to isokinetic leg strength exercises, does not influence fatigability, performance variables, or affective responses when compared with placebo (105855).
• Bladder cancer. Although there has been interest in using oral rhodiola for bladder cancer, there is insufficient reliable information about the clinical effects of rhodiola for this condition.
• Chronic fatigue syndrome (CFS). Although there has been interest in using oral rhodiola for CFS, there is insufficient reliable information about the clinical effects of rhodiola for this condition.
• Coronavirus disease 2019 (COVID-19). Oral rhodiola extract has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in adults a with confirmed history of COVID-19 infection and at least 3 of 9 long COVID-19 symptoms for at least 30 days, but no longer than 3 months, after discharge shows that taking a specific combination product (ADAPT-232/Chisan, Swedish Herbal Institute), containing rhodiola extract 90 mg, schisandra extract 300 mg, and eleuthero extract 78 mg, twice daily for 14 days increases walking duration by around 13 minutes but does not reduce the duration of cough, fatigue, headache, pain, or other respiratory problems when compared with placebo (109635). It is unclear if these findings are due to rhodiola, other ingredients, or the combination.
• Depression. It is unclear if oral rhodiola is beneficial for depression. Details: Clinical practice guidelines from the World Federation of Societies of Biological Psychiatry (WFSBP) and the Canadian Network for Mood and Anxiety Treatments (CANMAT) state that rhodiola is not currently recommended for monotherapy or adjunctive use in major depressive disorder based on mixed evidence (110318). Clinical research shows that taking a specific rhodiola extract (SHR-5, Swedish Herbal Institute) 340 mg once or twice daily reduces symptoms of mild-to-moderate depression after 6 weeks of treatment when compared with placebo. Rhodiola decreased overall depressive symptoms, emotional instability, insomnia, and somatization; however, it did not improve feelings of self-esteem (17616). Another small clinical study in patients with major depressive disorder of moderate severity shows that adding a higher dose of rhodiola 600 mg to sertraline daily for 12 weeks improves depressive symptoms when compared with either sertraline alone or sertraline with a lower dose of rhodiola (300 mg) (102283).
• Diabetes. Although there has been interest in using oral rhodiola for diabetes, there is insufficient reliable information about the clinical effects of rhodiola for this condition.
• Fatigue. Preliminary clinical research suggests that oral rhodiola extract decreases fatigue in stressful situations. Details: Most preliminary clinical trials have evaluated a specific rhodiola root extract (SHR-5, Swedish Herbal Institute) in various doses and populations. Taking 50 mg of this product twice daily reduces mental fatigue and improves subjective well-being in students during an examination period (1927). Taking 144 mg twice daily for 7 days reduces fatigue, but not stress, in university students (19287). In night shift workers, 170 mg daily for 2 weeks reduces feelings of fatigue and improves mental performance (6877). In military cadets, a single dose of 370-555 mg after 24 hours without sleep improves tests of mental processing and short-term memory (16411). Finally, taking 576 mg daily for 28 days decreases symptoms of fatigue and increases attention, but does not improve quality of life or symptoms of depression, in patients with stress-related fatigue (19286). Other clinical research shows that taking a different rhodiola root extract (Rhodaxon, Teknofarm), 660 mg daily for 20 days, reduces mental fatigue by 30% in first-year university students (19288). Clinical research using another specific dried rhodiola extract (Vitango, Schwabe Pharma) also shows that taking 200 mg twice daily for 12 weeks modestly reduces perceived levels of stress, burnout, and fatigue when compared to baseline in adults experiencing symptoms of burnout. The validity of these findings is limited by the lack of a control group (96459). Rhodiola extract has also been studied in combination schisandra berry extract and Siberian ginseng root extract (ADAPT-232, Swedish Herbal Institute). However, evidence is mixed, with one study showing that 270 mg daily improves attention, accuracy, and speed in tired individuals performing stressful cognitive tasks (19289), and another study showing that 280 mg daily for 7 days does not reduce mental fatigue or stress in university students (19287).
• Generalized anxiety disorder (GAD). It is unclear if oral rhodiola is beneficial for GAD. Details: A small clinical study shows that taking a specific rhodiola extract (Rhodax, Bodyonics Ltd.) 170 mg twice daily for 10 weeks decreases anxiety and depression and improves symptom scores when compared to baseline in patients with GAD (16410). The validity of these findings is limited by the lack of a comparator group.
• Hearing loss. Although there has been interest in using oral rhodiola for hearing loss, there is insufficient reliable information about the clinical effects of rhodiola for this purpose.
• Hyperlipidemia. Although there has been interest in using oral rhodiola for hyperlipidemia, there is insufficient reliable information about the clinical effects of rhodiola for this condition.
• Menopausal symptoms. Oral rhodiola has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in patients experiencing menopausal symptoms shows that taking a combination product (Menopause Relief EP, EuroPharma USA) containing rhodiola extract 400 mg and black cohosh extract 13 mg daily for 12 weeks improves psychological symptoms of menopause when compared with placebo or black cohosh alone (103269). It is unclear if these findings are due to rhodiola, black cohosh, or the combination.
• Premature ejaculation. Oral rhodiola has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in adults with lifelong premature ejaculation shows that taking a specific combination product (EndEP) containing rhodiola 200 mg, folic acid 200 mcg, zinc 10 mg, and biotin 50 mcg once daily for 90 days increases time to ejaculation by about 29 seconds and improves control of ejaculation in about 60% of participants when compared to baseline. These improvements disappear within 90 days of discontinuing treatment. The validity of these findings is limited by the lack of a control group (96460).
• Sexual arousal. Although there has been interest in using oral rhodiola for improving sexual arousal, there is insufficient reliable information about the clinical effects of rhodiola for this condition.
• Stress. Preliminary clinical research suggests that oral rhodiola extract reduces feelings of stress. Details: Preliminary clinical research in adults with general stress shows that taking a specific dried rhodiola extract (Vitango, Schwabe Pharma) modestly reduces levels of stress in certain situations. Taking 200 mg twice daily before breakfast and lunch for 4 weeks improves stress, disability, and functional impairment when compared to baseline (90431). A small study in college students with anxiety shows that taking 200 mg twice daily for 14 days modestly reduces reported levels of stress, anxiety, anger, confusion, and negative mood when compared to a control group (96462). In adults experiencing symptoms of burnout, taking this specific extract 200 mg twice daily for 12 weeks modestly reduces perceived levels of stress, burnout, and fatigue and improves sexual satisfaction when compared to baseline. The validity of these findings is limited by the lack of a control group (96459). Rhodiola has also been evaluated in combination with other ingredients in individuals with stress. A small clinical study in healthy adults with chronic stress shows that taking a specific combination product (Mg-Teadiola, Sanofi-Aventis), containing rhodiola extract 222 mg, magnesium 150 mg, green tea extract 125 mg (providing theanine 50 mg), vitamin B6 0.7 mg, vitamin B9 0.1 mg, and vitamin B12 1.25 mcg, daily for 4 weeks reduces stress scores when compared with placebo (108672). It is unclear if these findings are due to rhodiola, other ingredients, or the combination.
• Tuberculosis. Although there has been interest in using oral rhodiola for tuberculosis, there is insufficient reliable information about the clinical effects of rhodiola for this condition.
• Upper respiratory tract infection (URTI). Although there has been interest in using oral rhodiola for URTI prevention, there is insufficient reliable information about the clinical effects of rhodiola for this purpose. More evidence is needed to rate rhodiola for these uses.

(Read more about RHODIOLA)

POSSIBLY SAFE ...when used orally and appropriately, short-term. Ashwagandha has been used with apparent safety in doses of up to 1250 mg daily for up to 6 months (3710,11301,19271,90649,90652,90653,97292,101816,102682,102683) (102684,102685,102687,103476,105824,109586,109588,109589,109590). ...when used topically. Ashwagandha lotion has been used with apparent safety in concentrations up to 8% for up to 2 months (111538).

PREGNANCY: LIKELY UNSAFE
when used orally. Ashwagandha has abortifacient effects (12).

LACTATION:
Insufficient reliable information available; avoid using.

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LIKELY SAFE ...when used orally and appropriately, short-term. Eleuthero root extract 300-2000 mg has been used safely in clinical trials lasting up to 3 months (730,1427,2574,7522,11099,15586,91509). There is insufficient reliable information available about the safety of eleuthero when used long-term.

CHILDREN: POSSIBLY SAFE
when used orally in adolescents aged 12-17 years, short-term. Eleuthero 750 mg three times daily was used for 6 weeks with apparent safety in one clinical trial (75028). There is insufficient reliable information available about the safety of eleuthero in children or adolescents when used long-term.

PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.

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LIKELY SAFE ...when used orally in amounts commonly found in foods. Lavender has Generally Recognized as Safe (GRAS) status for food use in the US (4912).

POSSIBLY SAFE ...when used orally and appropriately in medicinal amounts (9792). In clinical research, a specific product containing lavender oil (Silexan, Dr Willmar Schwabe GmbH & Co. KG) has been used safely at doses of 80-160 mg daily for up to 10 weeks (58077,58080,58098,97257). Powdered dried lavender flowers 500 mg twice daily has also been used with apparent safety for up to 8 weeks (97256). ...when used topically and appropriately. Lavender oil has been used safely for up to 7 months in adults (5177,109858,109865). ...when the essential oil is inhaled as a part of aromatherapy. Clinical studies have used lavender oil aromatherapy with apparent safety for up to 12 weeks (7107,12213,16393,16394,95634,103062,103063,103065,103068).

CHILDREN: POSSIBLY SAFE
when the essential oil is inhaled as a part of aromatherapy. Clinical studies have used lavender oil aromatherapy with apparent safety in single doses for up to 2 minutes (109868).

CHILDREN: POSSIBLY UNSAFE
when applied topically in males. Anecdotal reports suggest that applying topical products containing lavender oil to prepubertal males may result in gynecomastia in some cases (15254,95643). Products with a higher concentration of lavender oil and more frequent applications might be more likely to result in gynecomastia.

PREGNANCY AND LACTATION:
Insufficient reliable evidence available. Preliminary clinical research shows that lavender essential oil can be inhaled during labor, with no apparent adverse outcomes in the infants (95633). Although this study suggests safety, high quality assessment of safety has not been conducted.

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POSSIBLY SAFE ...when used orally and appropriately, short-term. There is some clinical research showing that taking rhodiola extract up to 300 mg twice daily has been used without adverse effects for up to 12 weeks (13109,16410,17616,71172,96459,102283,103269).

PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.

(Read more about RHODIOLA)

ANTIDIABETES DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = B Theoretically, taking ashwagandha with antidiabetes drugs might increase the risk of hypoglycemia.  Details There is preliminary clinical evidence suggesting that ashwagandha might lower blood glucose levels. Theoretically, ashwagandha might have additive effects when used with antidiabetes drugs and increase the risk of hypoglycemia (19274,90649,102685).

ANTIHYPERTENSIVE DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, taking ashwagandha with antihypertensive drugs might increase the risk of hypotension.  Details Animal research suggests that ashwagandha might lower systolic and diastolic blood pressure (19279). Theoretically, ashwagandha might have additive effects when used with antihypertensive drugs and increase the risk of hypotension.

BENZODIAZEPINES Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, taking ashwagandha might increase the sedative effects of benzodiazepines.  Details There is preliminary evidence that ashwagandha might have an additive effect with diazepam (Valium) and clonazepam (Klonopin) (3710). This may also occur with other benzodiazepines.

CNS DEPRESSANTS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, taking ashwagandha might increase the sedative effects of CNS depressants.  Details Ashwagandha seems to have sedative effects. Theoretically, this may potentiate the effects of barbiturates, other sedatives, and anxiolytics (3710).

IMMUNOSUPPRESSANTS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, taking ashwagandha might decrease the effects of immunosuppressants.  Details Ashwagandha has demonstrated immunostimulant effects in humans (3710,3711,4114,11301,106786). Animal research has shown that ashwagandha can attenuate the immunosuppression caused by cyclophosphamide (3711,4114).

THYROID HORMONE Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = B Ashwagandha might increase the effects and adverse effects of thyroid hormone.  Details Concomitant use of ashwagandha with thyroid hormones may cause additive therapeutic and adverse effects. Preliminary clinical research and animal studies suggest that ashwagandha boosts thyroid hormone synthesis and secretion (19281,19282,97292). In one clinical study, ashwagandha increased triiodothyronine (T3) and thyroxine (T4) levels by 41.5% and 19.6%, respectively, and reduced serum TSH levels by 17.4% from baseline in adults with subclinical hypothyroidism (97292).

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ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, eleuthero may have antiplatelet effects and may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.  Details In vitro and animal research shows that a constituent of eleuthero, dihydroxybenzoic acid, appears to inhibit platelet aggregation (7592,74976). Concomitant use with anticoagulant or antiplatelet drugs might increase the risk of bleeding.

ANTIDIABETES DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = B Theoretically, eleuthero might have additive effects when used with antidiabetes drugs.  Details Animal research suggests that certain constituents of eleuthero have hypoglycemic activity in both healthy and diabetic animals (7591,73535,74932,74956,74988,74990). A small study in adults with type 2 diabetes also shows that taking eleuthero for 3 months can lower blood glucose levels (91509). However, one very small study in healthy individuals shows that taking powdered eleuthero 3 grams, 40 minutes prior to a 75-gram oral glucose tolerance test, significantly increases postprandial blood glucose levels when compared with placebo (12536). These contradictory findings might be due to patient-specific variability and variability in active ingredient ratios.

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, eleuthero might increase levels of drugs metabolized by CYP1A2.  Details In vitro and animal research suggest that standardized extracts of eleuthero inhibit CYP1A2 (7532). This effect has not been reported in humans.

CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, eleuthero might increase levels of drugs metabolized by CYP2C9.  Details In vitro and animal research suggest that standardized extracts of eleuthero might inhibit CYP2C9 (7532). This effect has not been reported in humans.

CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES Interaction Rating = Minor Be watchful with this combination. Severity = Moderate •  Occurrence = Unlikely •  Level of Evidence = B Theoretically, eleuthero might increase levels of drugs metabolized by CYP2D6.  Details In vitro and animal research suggest that standardized extracts of eleuthero might inhibit CYP2D6. However, research in healthy human volunteers has found that taking eleuthero 485 mg twice daily for 14 days does not inhibit CYP2D6 drug metabolism (7532,10400).

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES Interaction Rating = Minor Be watchful with this combination. Severity = Moderate •  Occurrence = Unlikely •  Level of Evidence = B Theoretically, eleuthero might increase levels of drugs metabolized by CYP3A4.  Details In vitro and animal research suggest that standardized extracts of eleuthero might inhibit CYP3A4. However, research in healthy human volunteers has found that taking eleuthero 485 mg twice daily for 14 days does not inhibit CYP3A4 drug metabolism (7532,10400).

DIGOXIN (Lanoxin) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Unlikely •  Level of Evidence = D Eleuthero might increase serum digoxin levels and increase the risk of side effects.  Details In one case report, a 74-year-old male who was stabilized on digoxin presented with an elevated serum digoxin level after starting an eleuthero supplement, without symptoms of toxicity. After stopping the supplement, serum digoxin levels returned to normal (543). It is not clear whether this was due to a pharmacokinetic interaction or to interference with the digoxin assay (15585). Although the product was found to be free of digoxin and digitoxin (543), it was not tested for other contaminants (797).

IMMUNOSUPPRESSANTS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, eleuthero might interfere with immunosuppressive drugs because of its immunostimulant activity.  Details Animal and in vitro research shows that eleuthero extracts have immunomodulatory effects, including increasing cellular and humoral activity (74887,74915).

ORGANIC ANION-TRANSPORTING POLYPEPTIDE SUBSTRATES (OATP) Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = D Theoretically, eleuthero might decrease levels of drugs metabolized by OATP.  Details In vitro research suggests that eleuthero inhibits OATP2B1, which might reduce the bioavailability of oral drugs that are substrates of OATP2B1 (35450). Due to the weak inhibitory effect identified in this study, this interaction is not likely to be clinically significant.

P-GLYCOPROTEIN SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, eleuthero might increase levels of P-glycoprotein substrates.  Details In vitro research suggests that eleuthero can inhibit the multi-drug transporter protein, P-glycoprotein (22639,91509). However, it is too soon to tell if this is clinically important. This interaction has not been reported in humans.

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CNS DEPRESSANTS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Unlikely •  Level of Evidence = D Theoretically, lavender might potentiate the therapeutic effects and adverse effects of CNS depressants.  Details Laboratory research suggests that lavender has sedative effects (7). However, clinical studies in patients taking oral lavender oil (Silexan) 160 mg for 10 weeks or taking lavender flower powder 1 gram daily for 2 months have not reported side effects of drowsiness, sedation, or sleepiness (97256,103061). There is still some concern that higher doses or different preparations of lavender might have additive effects with CNS depressant medications.

(Read more about LAVENDER)

ANTIDIABETES DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, taking rhodiola with antidiabetes drugs might increase the risk of hypoglycemia.  Details In vitro and animal research shows that rhodiola extract can decrease blood glucose due to alpha-glucosidase activity (15717,15719).

ANTIHYPERTENSIVE DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, taking rhodiola with antihypertensive drugs might increase the risk of hypotension.  Details In vitro and animal research shows that rhodiola extract inhibits angiotensin-converting enzyme (ACE) and might lower blood pressure (15719,19495).

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = B Theoretically, rhodiola might increase levels of drugs metabolized by CYP1A2.  Details In vitro research shows that rhodiola inhibits CYP1A2. This effect is highly variable and appears to be dependent on the rhodiola product studied (96461). However, a clinical study in healthy young males found that taking rhodiola extract 290 mg daily for 14 days does not inhibit the metabolism of caffeine, a CYP1A2 substrate (96463).

CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = B Theoretically, rhodiola might increase levels of drugs metabolized by CYP2C9.  Details In vitro research shows that rhodiola inhibits CYP2C9. This effect is highly variable and appears to be dependent on the rhodiola product studied (96461). Also, a clinical study in healthy young males found that taking rhodiola extract 290 mg daily for 14 days reduces the metabolism of losartan, a CYP2C9 substrate, by 21% after 4 hours (96463).

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = B Theoretically, rhodiola might increase levels of drugs metabolized by CYP3A4.  Details In vitro research shows that rhodiola inhibits CYP3A4 (19497,96461). This effect is highly variable and appears to be dependent on the rhodiola product studied (96461). However, a clinical study in healthy young males found that taking rhodiola extract 290 mg daily for 14 days does not inhibit the metabolism of midazolam, a CYP3A4 substrate (96463).

IMMUNOSUPPRESSANTS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, rhodiola use might interfere with immunosuppressive therapy.  Details In vitro and animal research show that rhodiola has immunostimulatory effects (19498,19499,19500,19501).

LOSARTAN (Cozaar) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = B Rhodiola might increase the levels and adverse effects of losartan.  Details A clinical study in healthy young males found that taking rhodiola extract 290 mg daily for 14 days reduces the metabolism of losartan, a CYP2C9 substrate, by 21% after 4 hours (96463).

P-GLYCOPROTEIN SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, rhodiola might increase levels of P-glycoprotein substrates.  Details In vitro research shows that rhodiola inhibits P-glycoprotein (19497). Theoretically, using rhodiola with P-glycoprotein substrates might increase drug levels and potentially increase the risk of adverse effects.

(Read more about RHODIOLA)

General ...Orally, ashwagandha seems to be well-tolerated. Topically, no adverse effects have been reported. However, a thorough evaluation of safety outcomes has not been conducted.
Most Common Adverse Effects:
Orally: Diarrhea, gastrointestinal upset, nausea, and vomiting. However, these adverse effects do not commonly occur with typical doses.
Serious Adverse Effects (Rare):
Orally: Some case reports raise concerns about acute liver failure, hepatic encephalopathy, and the need for liver transplantation with ashwagandha treatment.

Dermatologic ...Orally, dermatitis has been reported in three of 42 patients in a clinical trial (19276).

Endocrine ...A case report describes a 73-year-old female who had taken an ashwagandha root extract (unspecified dose) for 2 years to treat hypothyroidism which had been previously managed with levothyroxine. The patient was diagnosed with hyperthyroidism after presenting with supraventricular tachycardia, chest pain, tremor, dizziness, fatigue, irritability, hair thinning, and low thyroid stimulating hormone (TSH) levels. Hyperthyroidism resolved after discontinuing ashwagandha (108745).

Gastrointestinal ...Orally, large doses may cause gastrointestinal upset, diarrhea, and vomiting secondary to irritation of the mucous and serous membranes (3710). When taken orally, nausea and abdominal pain (19276,110490) and gastritis and flatulence (90651) have been reported.

Genitourinary ...In one case report, a 28-year-old male with a decrease in libido who was taking ashwagandha 5 grams daily over 10 days subsequently experienced burning, itching, and skin and mucous membrane discoloration of the penis, as well as an oval, dusky, eroded plaque (3 cm) with erythema on the glans penis and prepuce (32537).

Hepatic ...Orally, ashwagandha in doses of 154-1350 mg daily has played a role in several case reports of liver injury. In most of these cases, other causes of liver injury were excluded, and liver failure did not occur. Symptoms included jaundice, pruritus, malaise, fatigue, lethargy, weight loss, nausea, diarrhea, abdominal pain, stool discoloration, and dark urine. Symptom onset was typically 5-180 days from first intake, although in some cases onset occurred after more than 12 months of use (102686,107372,110490,110491,111533,111535,112111). Laboratory findings include elevated aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase, and serum bilirubin (112111). In most cases, liver enzymes normalized within 1-5 months after discontinuation of ashwagandha (102686,107372,110491,111535,112111). However, treatment with corticosteroids, lactulose, ornithine, ursodeoxycholic acid, and plasmapheresis, among other interventions, was required in one case (111533). Rarely, use of oral ashwagandha has been reported to cause hepatic encephalopathy and liver failure requiring liver transplantation (110490).

Neurologic/CNS ...Orally, ashwagandha has been reported to cause drowsiness (110492). Headache, neck pain, and blurry vision have been reported in a 47-year-old female taking ashwagandha, cannabis, and venlafaxine. Imaging over the course of multiple years and hospital admissions indicated numerous instances of intracranial hemorrhage and multifocal stenosis of intracranial arteries, likely secondary to reversible cerebral vasoconstriction syndrome (RCVS) (112113). It is unclear whether the RCVS and subsequent intracranial hemorrhages were precipitated by ashwagandha, cannabis, or venlafaxine.

(Read more about ASHWAGANDHA)

General ...Orally, eleuthero root is generally well tolerated when used short-term.
Most Common Adverse Effects:
Orally: Diarrhea, dyspepsia, gastrointestinal upset, headache, nausea, and urticaria.

Cardiovascular ...Orally, increased blood pressure has been reported in children with hypotension taking eleuthero in one clinical study (74980). Eleuthero has been reported to cause tachycardia, hypertension, and pericardial pain in patients with rheumatic heart disease or atherosclerosis. It is unclear if these effects were caused by eleuthero, or by the cardioglycoside-containing herb, silk vine (Periploca sepium), which is a common adulterant found in eleuthero products (12,797,6500).

Dermatologic ...Orally, eleuthero has been reported to cause rash in some clinical studies (75013,75028).

Gastrointestinal ...Orally, eleuthero has been reported to cause dyspepsia, nausea, diarrhea, and gastrointestinal upset in some patients (74938,75028,91510).

Genitourinary ...Orally, mastalgia and uterine bleeding were reported in 7. 3% of females taking eleuthero 2 grams daily in one clinical study (6500,11099). These adverse effects seem to be more likely with higher doses.

Neurologic/CNS ...Orally, headaches have been reported in 9. 8% of people taking eleuthero in one clinical study (11099).
In one case report, a 53-year-old female developed spontaneous subarachnoid hemorrhage associated with the use of an herbal supplement containing red clover, dong quai, and eleuthero (70419). It is unclear if this event was related to the use of eleuthero, the other ingredients, the combination, or another cause entirely.

Psychiatric ...Orally, nervousness has been reported in 7. 3% of people taking eleuthero in one clinical study (11099). Eleuthero has also been reported to cause slight anxiety, irritability, and melancholy in some patients (6500,11099). These adverse effects seem to be more likely to occur with higher doses.

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General ...Orally, lavender is well tolerated in food amounts and seems to be well tolerated in larger amounts. Topically, lavender oil seems to be well tolerated.
Most Common Adverse Effects:
Orally: Breath odor, constipation, diarrhea, dyspepsia, eructation, headache, and nausea.
Topically: Allergic contact dermatitis (with lavender oil).
Serious Adverse Effects (Rare):
Topically: Cases of gynecomastia have been reported in prepubertal males using lavender oil.

Cardiovascular ...Orally, a specific lavender oil ingredient (Silexan) has been associated with palpitations (103061).

Endocrine ...Topical products containing lavender oil alone, including a product referred to as agua de violetas, or in combination with tea tree oil have been linked to at least six cases of gynecomastia when used in prepubertal males. In each case, gynecomastia resolved when the lavender oil products were discontinued. It is thought that the estrogenic and antiandrogenic activity of lavender oil and tea tree oil resulted in gynecomastia in these cases (15254,95643).

Gastrointestinal ...Orally, lavender oil, including a specific lavender oil ingredient KG), may cause gastrointestinal disturbance, including dyspepsia, diarrhea, breath odor, eructation, and nausea (58077,58080,58098,93004,103061). Tincture of lavender has been linked to cases of constipation and increased appetite; however, it is unknown if this occurred at a greater rate than with placebo (9792).

Immunologic ...Topically, use of lavender oil, such as in personal care products, might cause allergic contact dermatitis in some patients (6,101728). There have been numerous case reports of allergic contact dermatitis and eczema linked to lavender oil exposure from shampoos, lotions, fragrances, or direct application of oil to pillows (10031,58043,58109,58120,101728).

Neurologic/CNS ...Orally, lavender flower powder, tincture of lavender containing 50% alcohol, and a specific lavender oil ingredient (Silexan) have been linked to headache (9792,103061,109860). Headache has also been reported rarely following lavender oil aromatherapy (109860).

Pulmonary/Respiratory ...In one case report, a 34-year-old Japanese female presented with complaints of dyspnea, cough, and fever 2 weeks after initiating lavender essential oil therapy via humidifier. The patient had an oxygen saturation of 88% and was diagnosed with acute eosinophilic pneumonia. Symptoms improved after a course of corticosteroids and discontinuation of aromatherapy (109979).

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General ...Orally, rhodiola seems to be well tolerated.
Most Common Adverse Effects:
Orally: Dizziness, increased or decreased production of saliva.

Gastrointestinal ...Orally, rhodiola extract may cause dry mouth or excessive saliva production (16410,16411).

Neurologic/CNS ...Orally, rhodiola extract can cause dizziness (16410).

(Read more about RHODIOLA)